12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer

      letter

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Long noncoding RNA HOTTIP plays important roles in the generation and progression of human cancers. Exosomes participate in cellular communication by transmitting moleculars between cells and are regarded as suitable candidates for non-invasive diagnosis. However, the existence of HOTTIP in the circulating exosomes and the potential roles of exosomal HOTTIP in gastric cancer (GC) was poorly understood. This study aims at investigating the clinical roles of exosomal HOTTIP in GC. Serum exosomal HOTTIP from 246 subjects (126 GC patients and 120 healthy people) were detected by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). Our results showed that expression levels of exosomal HOTTIP were typically upregulated in GC than in normal control ( P < 0.001). And its expression levels were significantly correlated with invasion depth ( P = 0.0298) and TNM stage ( P < 0.001). The AUC for exosomal HOTTIP was 0.827, which demonstrated a higher diagnostic capability than CEA, CA 19–9 and CA72–4 (AUC = 0.653, 0.685 and 0.639, respectively) ( P < 0.001). The Kaplan–Meier analysis showed a correlation between increased exosomal HOTTIP levels and poor overall survival (OS) (logrank P < 0.001). And univariate and multivariate COX analysis revealed exosomal HOTTIP overexpression was an independent prognostic factor in GC patients ( P = 0.027). These findings demonstrated that exosomal HOTTIP may be a potential biomarker for GC in diagnosis and prognosis.

          Electronic supplementary material

          The online version of this article (10.1186/s12943-018-0817-x) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references11

          • Record: found
          • Abstract: found
          • Article: not found

          Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.

          Exosomes are small vesicles (50-150 nm) of endocytic origin that are released by many different cell types. Exosomes in the tumor microenvironment may play a key role in facilitating cell-cell communication. Exosomes are reported to predominantly contain RNA and proteins. In this study, we investigated whether exosomes from pancreatic cancer cells and serum from patients with pancreatic ductal adenocarcinoma contain genomic DNA. Our results provide evidence that exosomes contain >10-kb fragments of double-stranded genomic DNA. Mutations in KRAS and p53 can be detected using genomic DNA from exosomes derived from pancreatic cancer cell lines and serum from patients with pancreatic cancer. In addition, using whole genome sequencing, we demonstrate that serum exosomes from patients with pancreatic cancer contain genomic DNA spanning all chromosomes. These results indicate that serum-derived exosomes can be used to determine genomic DNA mutations for cancer prediction, treatment, and therapy resistance.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Regulation of transcription by long noncoding RNAs.

            Over the past decade there has been a greater understanding of genomic complexity in eukaryotes ushered in by the immense technological advances in high-throughput sequencing of DNA and its corresponding RNA transcripts. This has resulted in the realization that beyond protein-coding genes, there are a large number of transcripts that do not encode for proteins and, therefore, may perform their function through RNA sequences and/or through secondary and tertiary structural determinants. This review is focused on the latest findings on a class of noncoding RNAs that are relatively large (>200 nucleotides), display nuclear localization, and use different strategies to regulate transcription. These are exciting times for discovering the biological scope and the mechanism of action for these RNA molecules, which have roles in dosage compensation, imprinting, enhancer function, and transcriptional regulation, with a great impact on development and disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer

              Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer-host cross talk. The aim of our study was to illustrate the clinical significance of the lncRNA CRNDE-h in exosomes purified from the serum of patients with colorectal cancer (CRC). The study was divided into four parts: (1) The exosome isolated methods and lncRNA detected methods which accurately and reproducibly measure CRC-related exosomal CRNDE-h in serum were optimized in preliminary pilot stage; (2) The stability of exosomal CRNDE-h was evaluated systematically; (3) The origin of exosomal CRNDE-h was explorated in vitro and in vivo; (4) The diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468 patients. In pilot study, our results indicated that exosomal CRNDE-h was detectable and stable in serum of CRC patients, and derived from tumor cells. Then, the increased expression of exosomal CRNDE-h was successfully validated in 148 CRC patients when compared with colorectal benign disease patients and healthy donors. Exosomal CRNDE-h level significantly correlated with CRC regional lymph node metastasis (P = 0.019) and distant metastasis (P = 0.003). Moreover, at the cut-off value of 0.020 exosomal CRNDE-h level of serum, the area under ROC curve distinguishing CRC from colorectal benign disease patients and healthy donors was 0.892, with 70.3% sensitivity and 94.4% specificity, which was superior to carcinoembryogenic antigen. In addition, high exosomal CRNDE-h level has a lower overall survival rates than that for low groups (34.6% vs. 68.2%, P < 0.001). In conclusion, detection of lncRNA CRNDE-h in exosome shed a light on utilizing exosomal CRNDE-h as a noninvasive serum-based tumor marker for diagnosis and prognosis of CRC.
                Bookmark

                Author and article information

                Contributors
                yizhang@sdu.edu.cn
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                27 February 2018
                27 February 2018
                2018
                : 17
                : 68
                Affiliations
                [1 ]ISNI 0000 0004 1761 1174, GRID grid.27255.37, Department of Clinical Laboratory, Qilu Hospital, , Shandong University, ; 107 Wenhua Xi Road, Jinan, Shandong 250012 China
                [2 ]Department of Clinical Laboratory, Shandong Provincial Third Hospital, Jinan, Shandong 250012 China
                Article
                817
                10.1186/s12943-018-0817-x
                6389063
                29486794
                ad28c6f9-385f-4fc3-934e-5c6c30a66afa
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 January 2018
                : 19 February 2018
                Funding
                Funded by: Shandong Key Research and Development Program
                Award ID: 2016GSF201122
                Award Recipient :
                Funded by: Shandong Key Research and Development Program
                Award ID: 2016CYJS01A02
                Award Recipient :
                Funded by: Taishan Scholar Foundation
                Funded by: FundRef http://dx.doi.org/10.13039/501100007129, Natural Science Foundation of Shandong Province;
                Award ID: ZR2017MH044
                Award Recipient :
                Funded by: Fundamental Research Funds of Shandong University
                Award ID: 2014QLKY03
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81601846
                Award Recipient :
                Categories
                Letter to the Editor
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                gastric cancer,long noncoding rna,hottip,diagnosis,prognosis
                Oncology & Radiotherapy
                gastric cancer, long noncoding rna, hottip, diagnosis, prognosis

                Comments

                Comment on this article